Model of Transport in Renal Medullary Microvasculature

肾髓微血管运输模型

• 批准号: 6805427
• 负责人: AURELIE EDWARDS
• 金额: $ 17.05万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6805427
• 关键词: electrolyte balance; hormone regulation /control mechanism; kidney circulation; lactates; mathematical model; membrane transport proteins; model design /development; nitric oxide; osmotic pressure; renal medulla; renal tubular transport; urea; water channel

DESCRIPTION (provided by applicant): The microcirculation in the renal medulla plays an essential role in the regulation of fluid and electrolyte excretion and in the long-term maintenance of arterial blood pressure. The overall goal of this research is to extend our mathematical model of the renal medullary microcirculation in order to understand the effects of specific transporters, osmolytes and hormones on medullary blood flow and its distribution. Our specific aims are as follows: Aim 1: To determine the importance of UTB urea transporters in providing a route for volume efflux that shunts blood flow from descending vasa recta (DVR) to ascending vasa recta (AVR), secondarily reducing blood flow to the inner medulla. We will incorporate new in vitro findings (including permeability and reflection coefficient measurements in UTB knockout mice) into our mathematical model in order to examine the role of water channels and urea transporters in regulating blood flow to the inner medulla. Aim 2: To examine the effects of the dependence of solute permeability on blood flow rate. Permeability of DVR to sodium and raffinose varies with perfusion rate; this dependence may be mediated by NO generation. We will investigate whether flow dependent increases in permeability reduce transmural concentration gradients and therefore water efflux from DVR, thereby enhancing blood flow to the inner medulla and decreasing concentrating ability. Aim 3: To determine whether lactate plays a significant role in the medullary microcirculation. It has been suggested that the accumulation of lactate could augment water removal from the thin descending limb and enable mathematical models to accurately predict cortico-medullary osmolality gradients. We will examine whether the presence of lactate can enhance volume efflux from DVR across transcellular pathways, thereby affecting blood flow to the papilla and axial small solute concentration gradients. Aim 4: To examine the effect of nitric oxide on overall medullary blood flow as well as on the distribution of blood flow between the inner medulla and the interbundle region of the outer medulla. We will investigate the extent to which NO generation may abrogate medullary hypoxia, and whether the production of nitric oxide by the thick ascending limb could constitute a feedback system aimed at specifically protecting the mTAL from ischemic injury, to the detriment of the inner medulla.

描述（由申请人提供）：肾髓质中的微循环在调节液体和电解质排泄以及长期维持动脉血压方面起着重要作用。本研究的总体目标是扩展我们的数学模型的肾髓质微循环，以了解特定的转运蛋白，渗透压和激素对髓质血流及其分布的影响。我们的具体目标如下： 目标1：确定UTB尿素转运蛋白在提供容量外排途径中的重要性，该途径将血流从直降血管（DVR）分流至直升血管（AVR），其次减少流向髓质内部的血流。我们将把新的体外研究结果（包括UTB基因敲除小鼠的渗透性和反射系数测量）纳入我们的数学模型，以研究水通道和尿素转运蛋白在调节内髓血流中的作用。 目的2：研究溶质渗透性对血流速度依赖性的影响。钠和棉子糖的DVR的渗透性随灌注速率而变化，这种依赖性可能是由NO的产生介导的。我们将研究是否流量依赖性增加的渗透性降低透壁浓度梯度，因此从DVR的水流出，从而提高血液流量的内部髓质和降低浓缩能力。 目的3：确定乳酸是否在延髓微循环中起重要作用。有人认为，乳酸的积累可以增加水从薄的下降肢体，使数学模型，以准确地预测皮质-髓质渗透压梯度。我们将研究乳酸盐的存在是否可以增强跨细胞途径从DVR的体积流出，从而影响到乳头和轴向小溶质浓度梯度的血流。 目标4：研究一氧化氮对整个髓质血流以及对内髓和外髓束间区域血流分布的影响。我们将研究NO产生在多大程度上可以消除髓质缺氧，以及粗升支产生的一氧化氮是否可以构成一个反馈系统，旨在特异性保护mTAL免受缺血性损伤，损害内部髓质。